Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner

SummaryMicroglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses.

► Microglia engulf presynaptic inputs undergoing active synaptic pruning ► Engulfment of developing synaptic inputs is dependent upon neural activity ► CR3/C3 signaling is necessary for microglia-mediated engulfment of synapses ► CR3/C3 signaling in microglia is required for proper synaptic connectivity